To test the hypothesis that activation of the ET_A receptor contributes to decreased renal excretory function and increased blood pressure in sensory nerve degenerated rats fed a high salt diet, neonatal Wistar rats were given vehicle or capsaicin (CAP, 50 mg/kg sc) on the first and second day of life. After weaning, vehicle or CAP-treated rats were fed a normal (NS, 0.5%) or a high (HS, 4%) sodium diet for 2 weeks with or without ABT-627 (5 mg/kg/day, an selective ET_A receptor antagonist). Systolic blood pressure increased in CAP-treated rats fed a HS diet (CAP-HS) compared to vehicle-treated rats fed a HS diet (CON-HS, 145 ± 7 vs. 89 ± 5 mmHg, p<0.05). Creatinine clearance and fractional sodium excretion (FE_Na) decreased in CAP-HS rats compared to CON-HS rats (creatinine clearance: 0.54 ± 0.05 vs. 0.81 ± 0.09 ml/min/100g body weight; FE_Na 8.68 ± 0.99 vs. 12.53 ± 1.47 %, respectively, p<0.05). Water and sodium balance increased in CAP-HS rats compared to CON-HS (water balance: 20.2 ± 1.5 vs. 15.5 ± 1.9 ml/day; sodium balance: 11.9 ± 3.1 vs. 2.4 ± 0.3 mEq/day, respectively, p<0.05). The ET-1 levels in plasma and isolated glomeruli increased by about twofold in CAP-HS rats compared to CON-HS rats (p<0.05). ABT-627 prevented the decrease in creatinine clearance and FE_Na, the increase in water and sodium balance, and the increase in blood pressure in CAP-HS rats (p<0.05). Therefore, blockade of the ET_A receptor ameliorates the impairment of renal excretory function and prevents the elevation in blood pressure in salt-sensitive hypertension induced by degeneration of sensory nerves, indicating that the activation of the ET_A receptor impairs renal function and contributes to the development of salt-induced increase in blood pressure in this model.